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Peripheral Blood Cytotoxic Lymphocyte Gene Transcript Levels Differ in Patients With Long-Term Type 1 Diabetes Compared to Normal Controls

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Abstract:

The purpose of this study was to compare mRNA levels of the cytotoxic lymphocyte (CL) gene products: granzyme B (GB), perforin (P), and fas ligand (FasL) in patients with long-term type 1 diabetes and healthy controls. The objective was to utilize this information to follow patients as they undergo islet cell transplantation at our center and to determine if changes in CL gene transcript levels correlate with graft status. We have measured mRNA levels for CL genes in peripheral blood samples from 65 long-term (>5 years) type 1 diabetes patients and 29 healthy controls. Total RNA was extracted from EDTA anticoagulated peripheral blood samples and reverse transcribed into first-strand cDNA using SuperScript II reverse Transcriptase. Quantitative, real-time PCR was utilized to determine CL gene transcript levels. mRNA levels of P and FasL genes were found to be significantly lower for patients with type 1 diabetes compared to normal controls (p < 0.05). However, there was no significant difference for GB mRNA levels between patients and controls (p > 0.05). The decreased expression of P and FasL in patients with long-term type 1 diabetes might contribute to the inability to maintain normal levels of peripheral tolerance, which is essential for protection from autoimmune disease.

Keywords: Cytotoxic lymphocyte genes; Fas ligand; Granzyme B; Perforin; Peripheral blood; Type 1 diabetes

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000005783982972

Affiliations: 1: Diabetes Research Institute, University of Miami School of Medicine, 1450 N.W. 10th Avenue, Miami, FL 33136, USA 2: Diabetes Research Institute, University of Miami School of Medicine, 1450 N.W. 10th Avenue, Miami, FL 33136, USA, Department of Medicine, University of Miami School of Medicine, 1450 N.W. 10th Avenue, Miami, FL 33136, USA 3: Beckman-Coulter Inc., Miami, FL 33136, USA

Publication date: June 1, 2005

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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